Obesity is by definition an enlargement of the adipose depot. Thus, this proposal will examine critical variables which are known to influence the development of adipose tissue in man and other animals. We will focus on the contributions of insulin, glucagon, and exercise in the development of adipose cellularity and obesity. How do these variables affect, how are they affected by food intake and insulin resistance in muscle and adipose tissue? These factors will be examined in genetically obese mice and rats and in rats made obese by force-feeding. Methods used include measurements of adipose cellularity by osmium fixation of adipocytes, study of the dynamics of insulin and glucagon release in isolated pancreatic islets, study of in vivo lipogenesis using tritiated water and measurements of the effects of insulin on in vitro glucose metabolism in muscle and adipose tissue. Finally food intake and activity patterns will be monitored in a small number of animals using a Digital PDP-11 minicomputer. The objective of this proposal is to elucidate the sequence of events that result in the production and maintainence of obesity in several different animal models. In this way we can assess the relative importance of such variables in the etiology of obesity. The ultimate objective is to utilize the knowledge in prevention and treatment of human obesity.